Gaucher’S Disease

(Gaucher’s disease)

Gaucher disease is a sphingolipidosis, an inherited metabolic disorder due to lack of glucocerebrosidase, which causes deposition of glucocerebroside and similar components. Symptoms and complaints vary with the type, but usually come hepatosplenomegaly or CNS changes before. The diagnosis is made by means of enzyme analysis in the white blood cells.

For more information, see Table sphingolipidosis.

Gaucher disease is a sphingolipidosis, an inherited metabolic disorder due to lack of glucocerebrosidase, which causes deposition of glucocerebroside and similar components. Symptoms and complaints vary with the type, but usually come hepatosplenomegaly or CNS changes before. The diagnosis is made by means of enzyme analysis in the white blood cells. For more information, see Table sphingolipidosis. See also approach in a patient with suspected congenital metabolic disorder The glucocerebrosidase normally hydrolyzed glucocerebroside from glucose to ceramide. The genetic enzyme deficiency leads to the accumulation of glucocerebroside in tissue macrophages by phagocytosis, forming so-called Gaucher cells. Accumulation of Gaucher cells in the perivascular space of the brain causes gliosis in the neuropathic structures. There are 3 types that differ in epidemiology, enzyme activity and manifestations. Type I (not neuropathic) is the most common type (90% of all patients). The remaining enzyme activity is highest. Ashkenazi Jews have the highest risk, one of 12 carriers. The onset of the disease ranges from 2 years to adulthood. Symptoms and complaints include hepatosplenomegaly, bone diseases (eg. As osteopenia, pain crises, osteolytic lesions with fractures), growth arrest, delayed puberty, hematoma and Lidspaltenflecke one. Epistaxis and hematoma due to thrombocytopenia, are common. The x-ray shows widened bone ends (Erlenmeyer flask-like) and a thinning of the cortex. Type II (acute, neuropathic) is very rare, and the remaining enzyme activity is the lowest. Onset is in infancy. The symptoms and complaints are a progressive, neurological deterioration (eg. As rigidity, seizures) and death with two years. Type III (subacute, neuropathic) falls in terms of incidence, enzyme activity and severity of clinical symptoms between type I and type II. The disease begins at any time during childhood. The clinical manifestations vary with the subtypes and include progressive dementia and ataxia (IIIa), bone and visceral involvement (Type IIIb) and supranuclear seizures with corneal opacity of the lens (type IIIc) a. Patients who survive until adolescence, can continue to live many years. Diagnostic enzyme analysis The diagnosis of Gaucher disease is provided by means of enzyme analysis in the white blood cells. Mutational analysis can identify carriers and distinguish the different types. Although a biopsy is unnecessary, the Gaucher cells – lipid-laden tissue macrophages in liver, spleen, lymph nodes, bone marrow, or the brain that have the appearance of crumpled paper, diagnostically. DNA analysis is performed more frequently. (See also check on suspicion of inherited metabolic disorders.) Therapy Type I and III: Enzyme replacement therapy with glucocerebrosidase Sometimes miglustat, Eliglustat, splenectomy or stem cell or bone marrow transplantation with enzyme replacement i.v. Glucocerebrosidase is effective for types I and III, for type II there is no treatment. The enzyme is modified for efficient transport to the lysosomes. Patients receiving enzyme replacement, require a routine HB- and platelet determining volumetric measurements of the spleen and liver by CT or MRI, as well as a routine examination for bone diseases caused by skeletal view DEXA scan or MRI. Miglustat (100 mg p.o. 3 times a day), a Glucosylceramidsynthasehemmer reduces the Glucocerebrosidkonzentration (the substrate of glucocerebrosidase) and is an alternative for patients who can not receive enzyme replacement. Eliglustat (84 mg po once / day or twice a day), another glucosylceramide synthase inhibitor, reduces the Glucocerebrosid- concentration. Splenectomy can help patients with anemia, leukopenia or thrombocytopenia, or if the spleen size is preparing complaints. Patients with anemia need blood transfusions. A bone marrow transplant or stem cell transplantation provides a safe cure, but is considered due to the increased morbidity and mortality as the last treatment option. Important points Gaucher disease is a sphingolipidosis due to lack of glucocerebrosidase, which causes an accumulation of glucocerebroside. There are 3 types that differ in epidemiology, enzyme activity and manifestations. Symptoms and complaints vary with the type, but usually come hepatosplenomegaly or CNS changes before. The diagnosis of Gaucher disease is carried out by enzyme analysis of leukocytes; Carriers are identified and the different types distinguished by mutation analysis. The treatment of Type I and III includes enzyme replacement with glucocerebrosidase and sometimes Miglustat, Eliglustat, splenectomy or stem cell or bone marrow transplantation; there is no treatment for type II.

Health Life Media Team

Leave a Reply